Emerging FMS-like tyrosine kinase 3 inhibitors for the treatment of acute myelogenous leukemia

Hillary Prescott, Hagop Kantarjian, Jorge Cortes, Farhad Ravandi

Research output: Contribution to journalReview article

8 Scopus citations

Abstract

The FMS-like tyrosine kinase 3 (FLT3) is highly expressed in acute leukemias. Mutations involving FLT3 are among the most common molecular abnormalities in acute myelogenous leukemia (AML). Available evidence suggests that these molecular lesions confer a shorter disease-free survival and overall survival in patients with intermediate-risk cytogenetics. Therefore, substantial interest in FLT3 as a therapeutic target has led to the development of several promising inhibitors that target this tyrosine kinase. Areas covered: This review covers the molecular pathways associated with FLT3 activation in patients with AML, the biological rationale for inhibiting FLT3 and recent clinical progress with FLT3 inhibitors for the treatment of AML. Six FLT3 inhibitors undergoing clinical evaluation are discussed. A review of selected published manuscripts on the subject of FLT3 inhibition in AML and a search of the English language manuscripts in PubMed using the index words FLT3 and AML were conducted and articles of interest selected. Expert opinion: Mutated forms of FLT3, specifically FLT3-internal tandem duplication, have a significant impact on the prognosis of AML patients, particularly those with a normal karyotype. Inhibiting FLT3 may lead to clinical benefit for patients with AML. Newly developed FLT3 inhibitors have shown encouraging activity as monotherapy and in combination with other therapeutic agents.

Original languageEnglish (US)
Pages (from-to)407-423
Number of pages17
JournalExpert Opinion on Emerging Drugs
Volume16
Issue number3
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

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Keywords

  • acute myelogenous leukemia
  • FLT3
  • FLT3 inhibitor
  • FLT3-ITD

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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